The molecular events concerned with the processes of initiation of DNA replication in small viruses will be investigated in the belief that these events are the most vulnerable place to selectively attack an invading virus once it is established and dividing within its host cell. The structure of the unique initiation region of the icosahedral coli phage DNA's (phi X174, G4 and STI) will be analyzed and the initiator proteins that interact with it will be purified, and their interaction analyzed. The mechanism of the viral induced shut down of host cell DNA synthesis will also be analyzed in the coli phage systems. The results will then be applied to studying ways of interfering with the DNA replication of the oncogenic viruses SV40 and polyoma.